An increased heart rate progressively increases the contractile force of the heart (Bowditch phenomenon). In this respect, in a normal heart the influx of calcium through the calcium channels is normally increased by high heart rate.
In humans, an increase in heart rate from 60 to 170 beats per minute stimulates developed force.
When the heart rate exceeds 170 beats per minute, the force developed by the ventricle begins to decrease.
If chronic heart failure and/or myopathic, valvulopathic or ischemic cardiomyopathy is present, this intrinsic property of the myocardium is partially or totally depressed, because of which the contractile force decreases for cardiac frequencies of the order of 100 bpm or even lower. The decompensated myocardium undergoes a phenotypic change with activity alteration of the enzymes which regulate calcium homeostasis: diastolic uptake and systolic release of calcium decrease and contractile performance improves only with bradycardia.
The heart rate starting from which the contractile force begins to decline diminishes progressively for known pathologies such as ischemic cardiomyopathy, diabetic cardiomyopathy, mitral regurgitation and dilated cardiomyopathy.
The optimum contraction rate, i.e. the rate corresponding to the strongest contractile force, varies for each pathology, for each different stage of the illness, and for each patient.
In these pathologies a decrease in the capacity of the ventricles to adapt to the greater requirement occurs, this decrease sometimes being defined as loss of ventricular pumping reserve; the contractile reserve loss is unable to support the increase in the function requirement which occurs during exercise.
It therefore happens that when pathologies are present, a compensated system, in which the greater function requirement is satisfied naturally by a positive force-frequency relationship, passes to a decompensated or unstable system, in which the force-frequency relationship is depressed, flattened or negative, i.e. the system responds to a disturbing event by amplifying the effect of the disturbance, and hence becomes unstable.
The deterioration and the possible inversion of the myocardial force-frequency relationship is a mechanism of conversion from a compensation situation to a cardiac decompensation situation in a diseased heart.
In advanced conditions of chronic heart failure the peak of the force-frequency relationship is sufficiently displaced towards low frequencies to produce a flattened or a negative slope on the rate spectrum between 80 and 160 beats per minute (bpm), which in practice is the entire spectrum of the chronic heart failure patient. This decrease in force as soon as the heart rate increases means that a sudden rate increase predisposes the ventricles to dilation because of venous overloading with increase in telediastolic pressure. Different therapies are known for remedying chronic heart failure, aimed at reducing heart rate to remedy the decrease in force with increase in rate, however the response of the individual therapies must be adapted to the particular conditions of the patient.
For example, therapy with beta blockers has proved effective in cardiomegaly regression and in improving the myocardial function in patients suffering from dilated cardiomyopathy, however patients do not respond uniformly to this therapy.
Because of the pejorative effect of inversion of the force-frequency relationship, one of the effectiveness components of therapy with beta blockers derives from the reduction in heart rate in itself.
If the bradycardia is sufficient to reposition the spectrum of heart operative frequencies to sufficiently low levels, the negative part of the force-frequency relationship is avoided.
The bradycardic action of beta blockers reduces the number of daily working phases of the heart in the negative part of the force-frequency relationship.
As the flattening and the descending limb of the force-frequency curve appears at different frequencies in the different types of cardiac decompensation and in different patients, the effectiveness of the action of beta blockers is variable.
To optimize chronic heart failure therapy, it therefore appears essential to identify in each patient the ascending part of the force-frequency curve and the specific rate which when exceeded initiates the flattening and the descending part, in order to optimize individual therapy for chronic heart failure.
The subsequent therapeutic action in an individual patient will be more advantageous the closer the negative part of the force-frequency curve lies to the basal heart rate.